{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:42:59Z","timestamp":1790775779612,"version":"4.1.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Mol Med"],"published-print":{"date-parts":[[2018,6]]},"DOI":"10.1038\/s12276-018-0099-9","type":"journal-article","created":{"date-parts":[[2018,6,6]],"date-time":"2018-06-06T07:44:27Z","timestamp":1528271067000},"page":"1-12","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["An MG53-IRS1-interaction disruptor ameliorates insulin resistance"],"prefix":"10.1038","volume":"50","author":[{"given":"Jun Sub","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Woon","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seonggu","family":"Ro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6002-5267","authenticated-orcid":false,"given":"Doyoung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Eun","family":"Na","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeoung-Ho","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Seon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bong-Woo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Gyu","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,6,6]]},"reference":[{"key":"99_CR1","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nrendo.2016.86","volume":"12","author":"AA Tahrani","year":"2016","unstructured":"Tahrani, A. A., Barnett, A. H. & Bailey, C. J. Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus. Nat. Rev. Endocrinol. 12, 566\u2013592 (2016).","journal-title":"Nat. Rev. Endocrinol."},{"key":"99_CR2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.5483\/BMBRep.2016.49.3.268","volume":"49","author":"DM Erion","year":"2016","unstructured":"Erion, D. M., Park, H. J. & Lee, H. Y. The role of lipids in the pathogenesis and treatment of type 2 diabetes and associated co-morbidities. BMB Rep. 49, 139\u2013148 (2016).","journal-title":"BMB Rep."},{"key":"99_CR3","doi-asserted-by":"crossref","first-page":"957","DOI":"10.2337\/diacare.31.11.957","volume":"31","author":"D Thiebaud","year":"1982","unstructured":"Thiebaud, D. et al. The effect of graded doses of insulin on total glucose uptake, glucose oxidation, and glucose storage in man. Diabetes 31, 957\u2013963 (1982).","journal-title":"Diabetes"},{"key":"99_CR4","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1172\/JCI111938","volume":"76","author":"RA DeFronzo","year":"1985","unstructured":"DeFronzo, R. A., Gunnarsson, R., Bjorkman, O., Olsson, M. & Wahren, J. Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus. J. Clin. Invest. 76, 149\u2013155 (1985).","journal-title":"J. Clin. Invest."},{"key":"99_CR5","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1038\/cdd.2010.1","volume":"17","author":"CS Lee","year":"2010","unstructured":"Lee, C. S. et al. TRIM72 negatively regulates myogenesis via targeting insulin receptor substrate-1. Cell Death Differ. 17, 1254\u20131265 (2010).","journal-title":"Cell Death Differ."},{"key":"99_CR6","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.bbrc.2010.04.072","volume":"396","author":"SY Jung","year":"2010","unstructured":"Jung, S. Y. & Ko, Y. G. TRIM72, a novel negative feedback regulator of myogenesis, is transcriptionally activated by the synergism of MyoD (or myogenin) and MEF2. Biochem. Biophys. Res. Commun. 396, 238\u2013245 (2010).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"99_CR7","volume":"4","author":"JS Yi","year":"2013","unstructured":"Yi, J. S. et al. MG53-induced IRS-1 ubiquitination negatively regulates skeletal myogenesis and insulin signalling. Nat. Commun. 4, 2354 (2013).","journal-title":"Nat. Commun."},{"key":"99_CR8","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1074\/jbc.M113.525154","volume":"289","author":"N Nguyen","year":"2014","unstructured":"Nguyen, N., Yi, J. S., Park, H., Lee, J. S. & Ko, Y. G. Mitsugumin 53 (MG53) ligase ubiquitinates focal adhesion kinase during skeletal myogenesis. J. Biol. Chem. 289, 3209\u20133216 (2014).","journal-title":"J. Biol. Chem."},{"key":"99_CR9","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nature11834","volume":"494","author":"R Song","year":"2013","unstructured":"Song, R. et al. Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders. Nature 494, 375\u2013379 (2013).","journal-title":"Nature"},{"key":"99_CR10","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/ncb1812","volume":"11","author":"C Cai","year":"2009","unstructured":"Cai, C. et al. MG53 nucleates assembly of cell membrane repair machinery. Nat. Cell Biol. 11, 56\u201364 (2009).","journal-title":"Nat. Cell Biol."},{"key":"99_CR11","doi-asserted-by":"crossref","first-page":"15894","DOI":"10.1074\/jbc.M109.009589","volume":"284","author":"C Cai","year":"2009","unstructured":"Cai, C. et al. Membrane repair defects in muscular dystrophy are linked to altered interaction between MG53, caveolin-3, and dysferlin. J. Biol. Chem. 284, 15894\u201315902 (2009).","journal-title":"J. Biol. Chem."},{"key":"99_CR12","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/mt.2012.5","volume":"20","author":"B He","year":"2012","unstructured":"He, B. et al. Enhancing muscle membrane repair by gene delivery of MG53 ameliorates muscular dystrophy and heart failure in delta-Sarcoglycan-deficient hamsters. Mol. Ther. 20, 727\u2013735 (2012).","journal-title":"Mol. Ther."},{"key":"99_CR13","doi-asserted-by":"crossref","first-page":"139ra185","DOI":"10.1126\/scitranslmed.3003921","volume":"4","author":"N Weisleder","year":"2012","unstructured":"Weisleder, N. et al. Recombinant MG53 protein modulates therapeutic cell membrane repair in treatment of muscular dystrophy. Sci. Transl. Med. 4, 139ra185 (2012).","journal-title":"Sci. Transl. Med."},{"key":"99_CR14","volume":"5","author":"Y Jia","year":"2014","unstructured":"Jia, Y. et al. Treatment of acute lung injury by targeting MG53-mediated cell membrane repair. Nat. Commun. 5, 4387 (2014).","journal-title":"Nat. Commun."},{"key":"99_CR15","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/mus.24160","volume":"49","author":"BT Corona","year":"2014","unstructured":"Corona, B. T. et al. Effect of recombinant human MG53 protein on tourniquet-induced ischemia-reperfusion injury in rat muscle. Muscle Nerve 49, 919\u2013921 (2014).","journal-title":"Muscle Nerve"},{"key":"99_CR16","doi-asserted-by":"crossref","first-page":"279ra236","DOI":"10.1126\/scitranslmed.3010755","volume":"7","author":"P Duann","year":"2015","unstructured":"Duann, P. et al. MG53-mediated cell membrane repair protects against acute kidney injury. Sci. Transl. Med. 7, 279ra236 (2015).","journal-title":"Sci. Transl. Med."},{"key":"99_CR17","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.yjmcc.2014.12.010","volume":"80","author":"J Liu","year":"2015","unstructured":"Liu, J. et al. Cardioprotection of recombinant human MG53 protein in a porcine model of ischemia and reperfusion injury. J. Mol. Cell. Cardiol. 80, 10\u201319 (2015).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"99_CR18","doi-asserted-by":"crossref","first-page":"22474","DOI":"10.18632\/oncotarget.7965","volume":"7","author":"Y Yao","year":"2016","unstructured":"Yao, Y. et al. MG53 permeates through blood-brain barrier to protect ischemic brain injury. Oncotarget 7, 22474\u201322485 (2016).","journal-title":"Oncotarget"},{"key":"99_CR19","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1111\/jcmm.13171","volume":"21","author":"W Yao","year":"2017","unstructured":"Yao, W. et al. MG53 anchored by dysferlin to cell membrane reduces hepatocyte apoptosis which induced by ischaemia\/reperfusion injury in vivo and in vitro. J. Cell. Mol. Med. 21, 2503\u20132513 (2017).","journal-title":"J. Cell. Mol. Med."},{"key":"99_CR20","doi-asserted-by":"crossref","first-page":"414","DOI":"10.5483\/BMBRep.2016.49.8.079","volume":"49","author":"T Tan","year":"2016","unstructured":"Tan, T., Ko, Y. G. & Ma, J. Dual function of MG53 in membrane repair and insulin signaling. BMB Rep. 49, 414\u2013423 (2016).","journal-title":"BMB Rep."},{"key":"99_CR21","doi-asserted-by":"crossref","first-page":"26627","DOI":"10.1074\/jbc.M116.754424","volume":"291","author":"H Lee","year":"2016","unstructured":"Lee, H. et al. MG53-IRS-1 (Mitsugumin 53-Insulin Receptor Substrate-1) interaction disruptor sensitizes insulin signaling in skeletal muscle. J. Biol. Chem. 291, 26627\u201326635 (2016).","journal-title":"J. Biol. Chem."},{"key":"99_CR22","doi-asserted-by":"crossref","first-page":"116","DOI":"10.5483\/BMBRep.2016.49.2.232","volume":"49","author":"H Lee","year":"2016","unstructured":"Lee, H. et al. Mitochondrial oxidative phosphorylation complexes exist in the sarcolemma of skeletal muscle. BMB Rep. 49, 116\u2013121 (2016).","journal-title":"BMB Rep."},{"key":"99_CR23","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.freeradbiomed.2017.08.016","volume":"112","author":"H Lee","year":"2017","unstructured":"Lee, H. et al. Extracellular reactive oxygen species are generated by a plasma membrane oxidative phosphorylation system. Free Radic. Biol. Med. 112, 504\u2013514 (2017).","journal-title":"Free Radic. Biol. Med."},{"key":"99_CR24","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/dmrr.2292","volume":"28","author":"LJ Berman","year":"2012","unstructured":"Berman, L. J., Weigensberg, M. J. & Spruijt-Metz, D. Physical activity is related to insulin sensitivity in children and adolescents, independent of adiposity: a review of the literature. Diabetes Metab. Res. Rev. 28, 395\u2013408 (2012).","journal-title":"Diabetes Metab. Res. Rev."},{"key":"99_CR25","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1249\/MSS.0b013e318295cdbb","volume":"45","author":"CK Roberts","year":"2013","unstructured":"Roberts, C. K., Little, J. P. & Thyfault, J. P. Modification of insulin sensitivity and glycemic control by activity and exercise. Med. Sci. Sports Exerc. 45, 1868\u20131877 (2013).","journal-title":"Med. Sci. Sports Exerc."},{"key":"99_CR26","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1056\/NEJMoa012512","volume":"346","author":"WC Knowler","year":"2002","unstructured":"Knowler, W. C. et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346, 393\u2013403 (2002).","journal-title":"N. Engl. J. Med."},{"key":"99_CR27","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.2337\/diabetes.51.7.2074","volume":"51","author":"N Musi","year":"2002","unstructured":"Musi, N. et al. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 51, 2074\u20132081 (2002).","journal-title":"Diabetes"},{"key":"99_CR28","doi-asserted-by":"crossref","first-page":"e100525","DOI":"10.1371\/journal.pone.0100525","volume":"9","author":"B Wessels","year":"2014","unstructured":"Wessels, B., Ciapaite, J., van den Broek, N. M., Nicolay, K. & Prompers, J. J. Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner. PLoS One 9, e100525 (2014).","journal-title":"PLoS One"},{"key":"99_CR29","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1042\/CS20110386","volume":"122","author":"B Viollet","year":"2012","unstructured":"Viollet, B. et al. Cellular and molecular mechanisms of metformin: an overview. Clin. Sci. (Lond.) 122, 253\u2013270 (2012).","journal-title":"Clin. Sci. (Lond.)"},{"key":"99_CR30","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/sj.bjp.0707452","volume":"153","author":"CE Quinn","year":"2008","unstructured":"Quinn, C. E., Hamilton, P. K., Lockhart, C. J. & McVeigh, G. E. Thiazolidinediones: effects on insulin resistance and the cardiovascular system. Br. J. Pharmacol. 153, 636\u2013645 (2008).","journal-title":"Br. J. Pharmacol."},{"key":"99_CR31","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1172\/JCI17305","volume":"112","author":"AW Norris","year":"2003","unstructured":"Norris, A. W. et al. Muscle-specific PPARgamma-deficient mice develop increased adiposity and insulin resistance but respond to thiazolidinediones. J. Clin. Invest. 112, 608\u2013618 (2003).","journal-title":"J. Clin. Invest."},{"key":"99_CR32","first-page":"E701","volume":"269","author":"LJ Mandarino","year":"1995","unstructured":"Mandarino, L. J. et al. Regulation of hexokinase II and glycogen synthase mRNA, protein, and activity in human muscle. Am. J. Physiol. 269, E701\u2013E708 (1995).","journal-title":"Am. J. Physiol."},{"key":"99_CR33","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.1073\/pnas.94.8.4171","volume":"94","author":"CM Rondinone","year":"1997","unstructured":"Rondinone, C. M. et al. Insulin receptor substrate (IRS) 1 is reduced and IRS-2 is the main docking protein for phosphatidylinositol 3-kinase in adipocytes from subjects with non-insulin-dependent diabetes mellitus. Proc. Natl Acad. Sci. USA 94, 4171\u20134175 (1997).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"99_CR34","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1172\/JCI119872","volume":"100","author":"NJ Kerouz","year":"1997","unstructured":"Kerouz, N. J., Horsch, D., Pons, S. & Kahn, C. R. Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob\/ob) mouse. J. Clin. Invest. 100, 3164\u20133172 (1997).","journal-title":"J. Clin. Invest."},{"key":"99_CR35","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1172\/JCI116060","volume":"90","author":"MJ Saad","year":"1992","unstructured":"Saad, M. J. et al. Regulation of insulin receptor substrate-1 in liver and muscle of animal models of insulin resistance. J. Clin. Invest. 90, 1839\u20131849 (1992).","journal-title":"J. Clin. Invest."},{"key":"99_CR36","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1093\/cvr\/cvu132","volume":"103","author":"Q Yu","year":"2014","unstructured":"Yu, Q. et al. Effective glycaemic control critically determines insulin cardioprotection against ischaemia\/reperfusion injury in anaesthetized dogs. Cardiovasc. Res. 103, 238\u2013247 (2014).","journal-title":"Cardiovasc. Res."},{"key":"99_CR37","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.atherosclerosis.2013.12.032","volume":"233","author":"S Nemoto","year":"2014","unstructured":"Nemoto, S., Matsumoto, T., Taguchi, K. & Kobayashi, T. Relationships among protein tyrosine phosphatase 1B, angiotensin II, and insulin-mediated aortic responses in type 2 diabetic Goto-Kakizaki rats. Atherosclerosis 233, 64\u201371 (2014).","journal-title":"Atherosclerosis"},{"key":"99_CR38","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1172\/JCI117909","volume":"95","author":"LJ Goodyear","year":"1995","unstructured":"Goodyear, L. J. et al. Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects. J. Clin. Invest. 95, 2195\u20132204 (1995).","journal-title":"J. Clin. Invest."},{"key":"99_CR39","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/372186a0","volume":"372","author":"E Araki","year":"1994","unstructured":"Araki, E. et al. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature 372, 186\u2013190 (1994).","journal-title":"Nature"},{"key":"99_CR40","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/372182a0","volume":"372","author":"H Tamemoto","year":"1994","unstructured":"Tamemoto, H. et al. Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature 372, 182\u2013186 (1994).","journal-title":"Nature"},{"key":"99_CR41","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/cvr\/cvw017","volume":"110","author":"FA Lemckert","year":"2016","unstructured":"Lemckert, F. A. et al. Lack of MG53 in human heart precludes utility as a biomarker of myocardial injury or endogenous cardioprotective factor. Cardiovasc. Res. 110, 178\u2013187 (2016).","journal-title":"Cardiovasc. Res."},{"key":"99_CR42","doi-asserted-by":"crossref","first-page":"E1170","DOI":"10.1210\/jc.2012-1162","volume":"97","author":"CH Chang","year":"2012","unstructured":"Chang, C. H., Lin, J. W., Wu, L. C., Lai, M. S. & Chuang, L. M. Oral insulin secretagogues, insulin, and cancer risk in type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 97, E1170\u2013E1175 (2012).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"99_CR43","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1002\/cncr.24465","volume":"115","author":"S Ognjanovic","year":"2009","unstructured":"Ognjanovic, S., Linabery, A. M., Charbonneau, B. & Ross, J. A. Trends in childhood rhabdomyosarcoma incidence and survival in the United States, 1975-2005. Cancer 115, 4218\u20134226 (2009).","journal-title":"Cancer"},{"key":"99_CR44","volume":"48","author":"J Hong","year":"2016","unstructured":"Hong, J. et al. Myosin heavy chain is stabilized by BCL-2 interacting cell death suppressor (BIS) in skeletal muscle. Exp. Mol. Med. 48, e225 (2016).","journal-title":"Exp. Mol. Med."}],"container-title":["Experimental & Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s12276-018-0099-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s12276-018-0099-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s12276-018-0099-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:09:43Z","timestamp":1684616983000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s12276-018-0099-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["99"],"URL":"https:\/\/doi.org\/10.1038\/s12276-018-0099-9","relation":{},"ISSN":["1226-3613","2092-6413"],"issn-type":[{"value":"1226-3613","type":"print"},{"value":"2092-6413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6]]},"assertion":[{"value":"9 November 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2018","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}